β‐lapachone Ameliorates Obesity through Enhancing Browning of White Adipose Tissue in High fat‐Diet Induced Obese Mice

Abstract

β‐laphachone (BLC) is a naphthoquinonea, originally isolated from a Bignoniaceae tree Tabebuia avellanedae Lorentz ex Griseb and has been extensively studied because it possesses a wide range of biological activities. However, the potential of BLC in the anti‐obesity has not been explored.This study was conducted to evaluate the anti‐obesity effect of BLC focusing on increasing in energy expenditure by browning effect of white adipocyte in stromal vascular fraction (SVF), and in diet induced obese mice model. BLC increased the expression of brown‐adipocyte specific genes, including UCP1, PRDM16, Cidea and PGC1α in SVF cell during differentiation. A significant increase of oxygen consumption rate (OCR) and higher degree of UCP1 was shown in BLC treated adipocyte. BLC decreased in body weight gains and reduced fat mass and adiposity compared to HFD. BLC also significantly increased fatty acid oxidation and mitochondrial function related genes in the liver, such as SIRT1, PGC1α, PPARα, UCP2 and CPT1. BLC also increased the resting VO2 and energy expenditure. Furthermore, BLC increases the expression of brown specific genes in WAT including UCP1, PRDM16, Cidea and PGC1α, and activates a brown adipocyte‐like transcriptional and functional phenotype in scWAT. Especially, the characteristics of morphological changes toward a BAT‐like phenotypes was shown in the scWAT of BLC fed mice. Taken together, increased expression of brown specific adipocyte genes significantly by BLC would lead to increase of energy expenditure by the browning of WAT and it prevents obesity and ameliorates metabolic disorders induced by obesity.